Method for the production of N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides and new intermediate products

ABSTRACT

The invention relates to a process for preparing N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides in which, in a first step, 2-amino-4,5-difluoro-benzonitrile is reacted with sulphonyl halides in the presence of an acid acceptor and in the presence of a diluent at temperatures between 0° C. and 150° C. and, in a second step, the N-(2-cyano-4,5-difluoro-phenyl)-sulphonamides and/or N-(2-cyano-4,5-difluoro-phenyl)-sulphonimides obtained in the first step are as pure substances or as mixtures with ammonia in the presence of a diluent reacted at a temperature between 100° C. and 200° C. The invention furthermore relates to novel intermediates of the process.

[0001] The invention relates to a novel process for preparingN-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides, which are known asintermediates in the preparation of herbicides, to novelN-(2-cyano-4,5-difluoro-phenyl)-sulphonamides andN-(2-cyano-4,5-difluoro-phenyl)-sulphonimides as intermediates for thisprocess and to processes for their preparation.

[0002] It is known that certainN-(5-amino-2-cyano-4-fluoro-phenyl)-alkanesulphonamides, such as, forexample, N-(5-amino-2-cyano-4-fluoro-phenyl)-methanesulphonamide, areobtained when corresponding halogenated benzene derivatives, such as,for example, 1-amino-4-cyano-2,5-difluoro-benzene, are heated withalkanesulphonamides, such as, for example, methanesulphonamide, in thepresence of an acid binder, such as, for example, potassium carbonate,and in the presence of a diluent, such as, for example,N-methyl-pyrrolidone (see EP-A-648772). However, this process affordsthe desired products in unsatisfactory yields. Accordingly, there is aneed for a more favourable preparation process forN-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides.

[0003] It has now been found thatN-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula(I)

[0004] in which

[0005] R represents in each case optionally substituted alkyl, alkenyl,alkinyl, cyclo-alkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl orheterocyclylalkyl

[0006] are obtained in high yields and in very good quality when, in afirst step, 2-amino-4,5-difluoro-benzonitrile of the formula (II)

[0007] is reacted with sulphonyl halides of the general formula (III)

X—SO₂—R  (III)

[0008] in which

[0009] R is as defined above and

[0010] X represents halogen

[0011] in the presence of an acid acceptor and in the presence of adiluent at temperatures between 0° C. and 150° C.

[0012] and the resulting N-(2-cyano-4,5-difluoro-phenyl)-sulphonamideintermediates of the general formula (IV) and/orN-(2-cyano-4,5-difluoro-phenyl)-sulphonimide intermediates of thegeneral formula (V)

[0013] in which

[0014] R is as defined above

[0015] are reacted as pure substances or as mixtures in a second stepwith ammonia in the presence of a diluent at temperatures between 100°and 200° C.

[0016] Surprisingly, theN-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula(I) can be obtained by the process according to the invention in arelatively simple manner in high yields and in very good quality, and apure end product can be prepared via a mixture of intermediates. Theintermediates of the formulae (IV) and (V) can be obtained as mixturesin virtually quantitative yield.

[0017] The main advantage of the process according to the invention isthe fact that the use of relatively expensive2,4,5-trifluoro-benzonitrile can be dispensed with, and the problematicexchange of a fluorine substituent for a sulphonylamino group is notnecessary.

[0018] The compound 2-amino-4,5-difluoro-benzonitrile of the formula(II) to be used as starting material has not yet been disclosed in theliterature; as a novel substance, it also forms part of thesubject-matter of the present invention.

[0019] The novel compound of the formula (II) is obtained when4,5-difluoro-2-nitro-benzonitrile of the formula (VI)

[0020] is reacted with a reducing agent which is customary forconverting aromatic nitro compounds into the corresponding aminocompounds, such as, for example, (a) hydrogen in the presence of acatalyst such as, for example, platinum or palladium (where the twolast-mentioned compounds are, if appropriate, “poisoned” and supportedon a carrier, such as, for example, activated carbon or bariumsulphate), in the presence of a diluent, such as, for example,tetrahydrofuran or dioxane, or (b) metals or metal salts, such as, forexample, tin, tin (II) chloride, iron (powder) in the presence of anacid, such as, for example, hydrochloric acid or acetic acid, and, ifappropriate, additionally in the presence of a diluent, such as, forexample, methanol or ethanol, at temperatures between 0° C. and 150° C.,preferably between 10° C. and 100° C. (cf. the Preparation Examples).

[0021] The intermediates of the formulae (IV) and (V) are not yet knownfrom the literature;

[0022] as novel substances, they also form part of the subject-matter ofthe present invention.

[0023] The 4,5-difluoro-2-nitro-benzonitrile of the formula (VI)required as precursor is already known (see JP 07070041- cited in Chem.Abstracts 123:111678). According to the patent literature cited,4,5-difluoro-2-nitro-benzonitrile can be prepared by reaction of2-bromo-4,5-difluoro-nitrobenzene with copper (I) cyanide inN,N-dimethyl-formamide.

[0024] However, the compound of the formula (VI) is also obtained when3,4-difluoro-benzonitrile is reacted with nitric acid, if appropriate inthe presence of sulphuric acid, at temperatures between −10° C. and +30°C. (cf. the Preparation Examples).

[0025] Surprisingly, this nitration proceeds in a very uniform manner(regioselectively), and hydrolysis of the cyano group, which is to beexpected under the nitration conditions, only occurs to a very lowextent.

[0026] The formula (III) provides a general definition of the sulphonylhalides further to be used as starting materials in the processaccording to the invention for preparingN-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula(I).

[0027] Preferred meanings in the formulae (I), (III), (IV) and (V) are:

[0028] R represents in each case optionally halogen-substituted alkyl,alkenyl or alkinyl having in each case up to 6 carbon atoms, representsin each case optionally halogen- or C₁-C₄-alkyl-substituted cycloalkylor cycloalkylalkyl having in each case 3 to 6 carbon atoms in thecycloalkyl group and, if appropriate, 1 to 4 carbon atoms in the alkylmoiety, represents in each case optionally nitro-, cyano-, halogen-,C₁-C₄-alkyl-, C₁-C₄-halogenoalkyl-, C₁-C₄-alkoxy-, C₁-C₄-halogenoalkoxy-or C₁-C₄-alkoxy-carbonyl-substituted aryl or arylalkyl having 6 or 10carbon atoms in the aryl group and, if appropriate, 1 to 4 carbon atomsin the alkyl moiety, or represents in each case optionally cyano-,halogen-, C₁-C₄-alkyl-, C₁-C₄-halogenoalkyl-, C₁-C₄-alkoxy- orC₁-C₄-halogenoalkoxy-substituted heterocyclyl or heterocyclylalkylhaving in each case 3 to 5 carbon atoms and 1 or 2 nitrogen atoms and/orone oxygen or sulphur atom in the heterocyclyl group and, ifappropriate, 1 to 4 carbon atoms in the alkyl moiety, and

[0029] X represents fluorine, chlorine or bromine.

[0030] Particularly preferred meanings in the above formulae are:

[0031] R represents in each case optionally fluorine- orchlorine-substituted methyl, ethyl, n- or i-propyl, n-, i-, s- ort-butyl, ethenyl, propenyl, butenyl, ethinyl, propinyl or butinyl,represents in each case optionally fluorine-, chlorine-, methyl- orethyl-substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl orcyclohexyl-methyl, represents in each case optionally nitro-, cyano-,fluorine-, chlorine-, bromine-, methyl-, ethyl-, n- or i-propyl-, n-,i-, s- or t-butyl-, tri-fluoromethyl-, methoxy-, ethoxy-, n- ori-propoxy-, n-, i-, s- or t-butoxy-, difluoromethoxy-,trifluoromethoxy-, methoxycarbonyl-, ethoxycarbonyl-, n- ori-propoxycarbonyl-substituted phenyl or benzyl, or represents in eachcase optionally cyano-, fluorine-, chlorine-, bromine-, methyl-, ethyl-,n- or i-propyl-, n-, i-, s- or t-butyl-, trifluoromethyl-, methoxy-,ethoxy-, n- or i-propoxy-, n-, i-, s- or t-butoxy-, difluoromethoxy- ortrifluoromethoxy-substituted heterocyclyl from the group consisting offuryl, thienyl, oxazolyl, isoxazolyl, pyrazolyl, pyridinyl andpyrimidinyl, and

[0032] X represents chlorine.

[0033] The starting materials of the formula (111) are known chemicalsfor synthesis.

[0034] The first step of the process according to the invention forpreparing N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of thegeneral formula (I) is carried out using an acid acceptor. Suitable acidacceptors are, in general, the customary inorganic or organic bases oracid acceptors. These preferably include alkali metal or alkaline earthmetal acetates, amides, carbonates, bicarbonates, hydrides, hydroxidesor alkoxides, such as, for example, sodium acetate, potassium acetate orcalcium acetate, lithium amide, sodium amide, potassium amide or calciumamide, sodium carbonate, potassium carbonate or calcium carbonate,sodium bicarbonate, potassium bicarbonate or calcium bicarbonate,lithium hydride, sodium hydride, potassium hydride or calcium hydride,lithium hydroxide, sodium hydroxide, potassium hydroxide or calciumhydroxide, sodium methoxide, ethoxide, n- or -i-propoxide, n-, i-, s- ort-butoxide or potassium methoxide, ethoxide, n- or i-propoxide, n-, i-,s- or t-butoxide; furthermore also basic organic nitrogen compounds,such as, for example, trimethylamine, triethylamine, tripropylamine,tributylamine, ethyl-diisopropylamine, N,N-dimethyl-cyclohexylamine,dicyclohexylamine, ethyl-dicyclohexylamine, N,N-dimethyl-aniline,N,N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-,2,4-dimethyl-, 2,6-dimethyl-, 3,4-dimethyl- and 3,5-dimethyl-pyridine,5-ethyl-2-methyl-pyridine, 4-dimethylamino-pyridine,N-methyl-piperidine, 1,4-diazabicyclo[2.2.2]-octane (DABCO),1,5-diazabicyclo[4.3.0]-non-5-ene (DBN) or1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU).

[0035] Preferred acid acceptors are basic organic nitrogen compounds.

[0036] Suitable diluents for carrying out the first step of the processaccording to the invention are, especially, inert organic solvents.These include, in particular, aliphatic, alicyclic or aromatic,optionally halogenated hydrocarbons, such as, for example, benzine,benzene, toluene, xylene, chlorobenzene, dichlorobenzene. petroleumether, hexane, cyclohexane, dichloromethane, chloroform, carbontetrachloride; ethers, such as diethyl ether, diisopropyl ether,dioxane, tetrahydrofuran or ethylene glycol dimethyl ether or ethyleneglycol diethyl ether; ketones, such as acetone, butanone or methylisobutyl ketone; nitriles, such as acetonitrile, propionitrile orbutyronitrile; amides, such as N,N-dimethylformamide,N,N-dimethylacetamide, N-methyl-form anilide, N-methyl-pyrrolidone orhexamethylphosphoric triamide; esters, such as methyl acetate or ethylacetate, sulphoxides, such as dimethyl sulphoxide.

[0037] Preferred diluents are aprotic polar organic solvents, inparticular acetone or acetonitrile, or else basic organic nitrogencompounds, such as pyridine or 5-ethyl-2-methyl-pyridine.

[0038] When carrying out the first step of the process according to theinvention, the reaction temperatures can be varied within a relativelywide range. In general, the first step is carried out at temperaturesbetween 0° C. and 150° C., preferably between 110° C. and 120° C.

[0039] The first step of the process according to the invention isgenerally carried out under atmospheric pressure. However, it is alsopossible to carry out the process according to the invention underelevated or reduced pressure—generally between 0.1 bar and 10 bar.

[0040] For carrying out the first step of the process according to theinvention, generally between 1 mol and 10 mol, preferably between 2 moland 5 mol, of sulphonyl halide of the general formula (III) and between1 mol and 10 mol, preferably between 2 mol and 5 mol, of acid acceptorare employed per mole of 2-amino-4,5-difluoro-benzonitrile of theformula (II).

[0041] In a preferred embodiment of the first step of the processaccording to the invention, thc 2-amino-4,5-difluoro-benzonitrile of theformula (II) is initially charged together with an acid acceptor and adiluent, and the sulphonyl halide of the general formula (III) is thenslowly metered into this mixture with stirring—and, if appropriate, withcooling. The complete reaction mixture is then—if appropriate atelevated temperature—stirred until the reaction has ended.

[0042] The mixture of the intermediates of the formulae (IV) and (V) canbe worked up in a customary manner. The mixture is, for example, stirredwith water or a dilute aqueous acid, the organic phase is separated off,the aqueous phase is, if appropriate, reextracted with an organicsolvent which is virtually water-miscible, such as, for example, ethylacetate, and the combined organic phases are dried and filtered. Toisolate the mixture of intermediates, the solvent is carefully distilledoff under reduced pressure from the filtrate.

[0043] The resulting mixtures of the intermediates of the formulae (IV)and (V) can advantageously be employed without any further purificationfor the reaction according to the second step of the process accordingto the invention.

[0044] The second step of the process according to the invention ispreferably carried out using a diluent. Suitable diluents are,especially, inert organic solvents. These include, in particular,aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons,such as, for example, benzine, benzene, toluene, xylene, chlorobenzene,dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane,chloroform, carbon tetrachloride; ethers, such as diethyl ether,diisopropyl ether, t-butyl methyl ether, t-pentyl methyl ether, dioxane,tetrahydrofuran or ethylene glycol dimethyl ether or ethylene glycoldiethyl ether; ketones, such as, acetone, butanone or methyl isobutylketone; nitriles, such as acetonitrile, propionitrile or butyronitrile;amides, such as N,N-dimethylformamide, N,N-dimethylacetamide,N-methyl-formanilide, N-methyl-pyrrolidone or hexamethylphosphorictriamide; esters, such as methyl acetate or ethyl acetate, sulphoxides,such as dimethyl sulphoxide.

[0045] Preference is given to using, as diluents, aprotic polar organicsolvents, in particular diisopropyl ether, t-butyl methyl ether,t-pentyl methyl ether, tetrahydrofuran, dioxane, ethylene glycoldimethyl ether or ethylene glycol diethyl ether.

[0046] When carrying out the second step of the process according to theinvention, the reaction temperatures can be varied within a relativelywide range. In general, the second step is carried out at temperaturesbetween 50° C. and 200° C., preferably between 100° C. and 180° C.

[0047] The second step of the process according to the invention isgenerally carried out in a closed reaction vessel (in particular in anautoclave) under elevated pressure, the pressure depending on the settemperature and the solvent used.

[0048] For carrying out the second step of the process according to theinvention, generally between 1 and 100 mol, preferably between 5 and 50mol, of ammonia are employed per mole of the sum of the intermediates ofthe formulae (IV) and (V).

[0049] In a preferred embodiment of the second step of the processaccording to the invention, the reaction components of the formula (IV)and/or (V) are mixed at room temperature (about 20° C.) with ammonia anda diluent and heated in a closed reaction vessel until the reaction hasended.

[0050] Work-up and isolation of the products of the formula (I) can becarried out by customary methods. The reaction mixture is, for example,filtered after cooling, and the solvent is carefully distilled off underreduced pressure from the filtrate. The product can be obtained in thismanner as a residue, generally in good quality.

[0051] The compounds of the formula (I) preparable by the processaccording to the invention can be employed as intermediates forpreparing herbicidally active compounds (see EP-A-648749, EP-A-648772,WO-A-95/29158).

[0052] The intermediates of the formulae (IV) and (V) can also be usedas precursors for preparing herbicides (see EP-A 609734).

PREPARATION EXAMPLES

[0053]

[0054] 15 g (130 mmol) of methanesulphonyl chloride are added dropwisewith stirring to a mixture of 3.7 g (24 mmol) of2-amino-4,5-difluoro-benzonitrile, 5.0 g (33 mmol) of1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) and 50 ml of pyridine, and thereaction mixture is then heated at 50° C. for approximately one hour.The mixture is subsequently concentrated under water pump vacuum, theresidue is stirred with 100 ml of 20% strength hydrochloric acid and 10ml of ethyl acetate and the crystalline product is isolated byfiltration with suction.

[0055] This gives 3.3 g (44% of theory) of4,5-difluoro-2-(bis-methanesulphonyl-amino)-benzonitrile of meltingpoint 144° C.

[0056] In a 100 ml autoclave, 2 ml of ammonia are condensed and 2.0 g(6.4 mmol) of 4,5-difluoro-2-(bis-methanesulphonyl-amino)-benzonitrileand 40 ml of tetrahydrofuran are added. The reaction mixture is thenheated in the closed autoclave at 150° C. for 15 hours. After cooling,the mixture is filtered and the filtrate is concentrated under waterpump vacuum. Washing with 2N hydrochloric acid and with water gives 0.50g (34% of theory) ofN-(5-amino-2-cyano-4-fluoro-phenyl)-methanesulphonamide of melting point235° C.

[0057] 4.6 g (40 mmol) of methanesulphonyl chloride are added dropwisewith stirring to a mixture of 1.54 g (10 mmol) of2-amino-4,5-difluoro-benzonitrile, 4.0 g (40 mmol) of triethylamine and50 ml of acetonitrile, and the complete reaction mixture is then heatedunder reflux for approximately one hour. After cooling, the mixture isstirred with 100 ml of ice-water for 30 minutes, the phases areseparated and the aqueous phase is reextracted with 50 ml of ethylacetate. The combined organic phases are washed with saturated aqueousammonium bicarbonate solution and then with water, dried using sodiumsulphate and filtered. The solvent is carefully distilled off from thefiltrate under water pump vacuum.

[0058] This gives 2.9 g of a mixture of 43% of4,5-difluoro-2-(bis-methyl-sulphonylamino)-benzonitrile and 57% of4,5-difluoro-2-methylsulphonylamino-benzonitrile (according to GC/MS) asresidue, corresponding to a quantitative overall yield.

[0059] In a 100 ml autoclave, 4.5 ml of ammonia are condensed and theproduct mixture obtained according to step 2 (2.9 g) and 50 ml oftetrahydrofuran are added. The reaction mixture is then heated in theclosed autoclave at 150° C. for 15 hours. After cooling, the mixture isfiltered and the filtrate is concentrated under water pump vacuum.Washing with 2N hydrochloric acid and with water gives 1.0 g (44% oftheory) of N-(5-amino-2-cyano-4-fluoro-phenyl)-methanesulphonamide ofmelting point 235° C.

[0060] 5.1 g (40 mmol) of ethanesulphonyl chloride are added dropwisewith stirring to a mixture of 1.54 g (10 mmol) of2-amino-4,5-difluoro-benzonitrile, 4.0 g (40 mmol) of triethylamine and50 ml of acetonitrile, and the complete reaction mixture is then heatedunder reflux for approximately two hours. After cooling, the mixture isstirred with 100 ml of ice-water for 30 minutes, the phases areseparated and the aqueous phase is reextracted with 50 ml of ethylacetate. The combined organic phases are dried using sodium sulphate andfiltered. The solvent is carefully distilled off from the filtrate underwater pump vacuum. This gives 3.0 g of a mixture of 67% of4,5-difluoro-2-(bis-ethyl-sulphonylamino)-benzonitrile and 33% of4,5-difluoro-2-ethylsulphonylamino-benzonitrile (according to GC/MS) asresidue, corresponding to a quantitative overall yield.

[0061] In a 100 ml autoclave, 4 ml of ammonia are condensed and 3.0 g ofthe product mixture from Step 1 and 50 ml of tetrahydrofuran are added.The reaction mixture is heated in the closed autoclave at 150° C. for 15hours and, after cooling, filtered. The filtrate is concentrated underwater pump vacuum, washed with 2N hydrochloric acid and with water anddried.

[0062] This gives 1.1 g (45% of theory of a 95.5% pure product) of4-amino-5-fluoro-2-ethylsulphonylamino-benzonitrile of melting point170° C.

[0063] Starting Material of the Formula (II)

EXAMPLE (II-1)

[0064]

[0065] 3.68 g (20 mmol) of 4,5-difluoro-2-nitro-benzonitrile aredissolved in 40 ml of dioxane, and 300 mg of platinum on carbon (5%) areadded. The suspension is subsequently stirred under hydrogen at from 20°C. to 25° C. until 1.45 liters of hydrogen have been taken up. Themixture is then filtered through silica gel and the filtrate isconcentrated under water pump vacuum. The residue is then worked up bycolumn chromatography (silica gel, hexane/ethyl acetate).

[0066] This gives 2.19 g (72% of theory) of2-amino-4,5-difluoro-benzonitrile of melting point 114° C. and, fromanother fraction 0.52 g (15% of theory) of2-amino-4,5-difluoro-benzamide.

EXAMPLE (II-2)

[0067]

[0068] 11.0 g (59 mmol) of 4,5-difluoro-2-nitro-benzonitrile aredissolved in 175 ml of acetic acid (“glacial acetic acid”), and 20 g(358 mmol) of iron (powder) are added a little at a time. During theaddition, the reaction temperature is kept at from 40° C. to 50° C. bycooling using a water bath. The complete reaction mixture is thenstirred at

[0069] 50° C. for another 3 hours. After cooling to room temperature,the mixture is poured into 200 ml of ice-water. The mixture is extractedtwice with 50 ml of ethyl acetate each time, and the organic extractsolutions are combined, washed with saturated sodium bicarbonatesolution and then with water, dried with sodium sulphate and filtered.The filtrate is concentrated under water pump vacuum and the residue isworked up by column chromatography (silica gel, hexane/ethyl acetate).

[0070] This gives 7.7 g (85% of theory) of2-amino-4,5-difluoro-benzonitrile of melting point 114° C.

[0071] Starting Material of the Formula (VI):

EXAMPLE (VI-1)

[0072]

[0073] A mixture of 40 ml of sulphuric acid (97% strength) and 30 ml ofnitric acid (98% strength) is cooled to 0° C. 13.9 g (0.10 mol) of3,4-difluoro-benzonitrile are then added a little at a time such thatthe reaction temperature stays below 5° C. The complete reaction mixtureis stirred at from 5° C. to 10° C. for 5 hours and, after warming to 20°C., stirred for another 2 hours. The mixture is subsequently poured onto400 g of ice, and the crystalline product is isolated by filtration withsuction and taken up in 20 ml of methylene chloride. The aqueous phaseis reextracted twice using 30 ml of methylene chloride each time. Theorganic phases are combined, washed with saturated sodium bicarbonatesolution and with water, dried with sodium sulphate and filtered. Thesolvent is carefully distilled off from the filtrate under water pumpvacuum.

[0074] This gives 10.2 g (55% of theory) of4,5-difluoro-2-nitro-benzonitrile of melting point 75° C.

1. Process for preparingN-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula(I)

in which R represents in each case optionally substituted alkyl,alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl,heterocyclyl or heterocyclylalkyl, characterized by the following steps:A) reaction of 2-amino-4,5-difluoro-benzonitrile of the formula (II)

 with sulphonyl halides of the general formula (III) X—SO₂—R  (III)  inwhich R is as defined above and X represents halogen  in the presence ofan acid acceptor and in the presence of a diluent at temperaturesbetween 0° C. and 150° C. and B) reaction of theN-(2-cyano-4,5-difluoro-phenyl)sulphonamides of the general formula (IV)and/or N-(2-cyano-4,5-difluoro-phenyl)-sulphonimides of the generalformula (V) obtained in step A)

 in which R is as defined above  as pure substances or as mixtures withammonia in the presence of a diluent at temperatures between 100° and200° C.
 2. Process according to claim 1, characterized in that Rrepresents in each case optionally halogen-substituted alkyl, alkenyl oralkinyl having in each case up to 6 carbon atoms, represents in eachcase optionally halogen- or C₁-C₄-alkyl-substituted cycloalkyl orcycloalkylalkyl having in each case 3 to 6 carbon atoms in thecyclo-alkyl group and, if appropriate, 1 to 4 carbon atoms in the alkylmoiety, represents in each case optionally nitro-, cyano-, halogen-,C₁-C₄-alkyl-, C₁-C₄-halogenoalkyl-, C₁-C₄-alkoxy-, C₁-C₄-halogenoalkoxy-or C₁-C₄-alkoxy-carbonyl-substituted aryl or arylalkyl having 6 or 10carbon atoms in the aryl group and, if appropriate, 1 to 4 carbon atomsin the alkyl moiety, or represents in each case optionally cyano-,halogen-, C₁-C₄-alkyl-, C₁-C₄-halogenoalkyl-, C₁-C₄-alkoxy- orC₁-C₄-halogenoalkoxy-substituted heterocyclyl or heterocyclylalkylhaving in each case 3 to 5 carbon atoms and 1 or 2 nitrogen atoms and/orone oxygen or sulphur atom in the heterocyclyl group and, ifappropriate, 1 to 4 carbon atoms in the alkyl moiety, and X representsfluorine, chlorine or bromine.
 3. Process according to claim 2,characterized in that R represents in each case optionally fluorine- orchlorine-substituted methyl, ethyl, n- or i-propyl, n-, i-, s- ort-butyl, ethenyl, propenyl, butenyl, ethinyl, propinyl or butinyl,represents in each case optionally fluorine-, chlorine-, methyl- orethyl-substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl orcyclohexylmethyl, represents in each case optionally nitro-, cyano-,fluorine-, chlorine-, bromine-, methyl-, ethyl-, n- or i-propyl-, n-,i-, s- or t-butyl-, trifluoromethyl-, methoxy-, ethoxy-, n- ori-propoxy-, n-, i-, s- or t-butoxy-, difluoromethoxy-,trifluoromethoxy-, methoxycarbonyl-, ethoxycarbonyl-, n- ori-propoxycarbonyl-substituted phenyl or benzyl, or represents in eachcase optionally cyano-, fluorine-, chlorine-, bromine-, methyl-, ethyl-,n- or i-propyl-, n-, i-, s- or t-butyl-, trifluoromethyl-, methoxy-,ethoxy-, n- or i-propoxy-, n-, i-, s- or t-butoxy-, difluoromethoxy- ortrifluoromethoxy-substituted hetero-cyclyl from the group consisting offuryl, thienyl, oxazolyl, isoxazolyl, pyrazolyl, pyridinyl andpyrimidinyl, and X represents chlorine.
 4. Process according to any ofclaims 1 to 3, characterized in that the acid acceptors used are basicorganic nitrogen compounds.
 5. Process according to any of claims 1 to4, characterized in that the diluent used in step A) is acetone and/oracetonitrile and the diluent used in step B) is pyridine and/or5-ethyl-2-methyl-pyridine.
 6. 2-Amino-4,5-difluoro-benzonitrile. 7.Process for preparing 2-amino-4,5-difluoro-benzonitrile, characterizedin that 4,5-difluoro-2-nitro-benzonitrile is reacted with a reactantwhich is customary for converting aromatic nitro compounds into thecorresponding amino compounds, at temperatures between 0° C. and 150° C.8. N-(2-Cyano-4,5-difluoro-phenyl)-sulphonamides of the general formula(IV)

in which R is as defined in any of claims 1 to
 3. 9.N-(2-Cyano-4,5-difluoro-phenyl)-sulphonamides of the general formula (V)

in which R is as defined in any of claims 1 to 3.